The objective of our Cerebral Vascular Disease Research Center at the University of Miami is to carry out a program of integrated multi- disciplinary experimental research into the mechanisms and therapies of ischemic brain injury. The ultimate goal of our program is to identify factors responsible for ischemic injury which may be amenable to therapeutic or prophylactic intervention. The Program Project consists of four investigative proposals supported by Core facilities in the areas of molecular biology, metabolite and neurotransmitter analysis, animal physiology, neuropathology, tracer-kinetic radioisotopic strategies, computer applications, image-processing and animal neurobehavior. The computer/image-processing core has pioneered in the development of three-dimensional autoradiographic image-averaging and has just been expanded via an NIH Shared Instrumentation award. Molecular biological approaches include in situ hybridization for glutamate receptor subtypes and growth factors, and mRNA differential display for novel gene expression following ischemia. The cores contribute substantively to the implementation of each Project and unify the Projects by common methodological approaches. Project areas include: (1) focal cerebral ischemia: pathophysiology, acute therapy and recovery of function; (2) cellular and molecular mechanisms involved in early and delayed injury following global cerebral ischemia; (3) delayed hyperthermic triggering of irreversible injury following global and focal ischemia: hemodynamic, biochemical and molecular mechanisms; and (4) functional impairment and recovery after cortical infarction: metabolic, anatomical and molecular mechanisms. The Projects are conceptually closely integrated with one another and are strongly supported by close collaborative interactions among investigators.